Tolerable Upper Intake Level of Iron Damages the Intestine and Alters the Intestinal Flora in Weaned Piglets
Abstract
Iron supplementation has been an intervention to improve iron storage and prevent iron deficiency anemia in weaned piglets and the recommended nutrient intake (RNI) and tolerable upper intake levels (UL) of iron have been established. The purpose of this study is to investigate the potential harm of UL iron to the gut and microbes of weaned piglets. Thirty 23 day old weaned piglets were assigned to three dietary treatments: a basal diet supplemented with 100 (RNI), 300, and 3000 (UL) mg FeSO4 per kg diet for 28 days. Then, we used the intestinal porcine epithelial cell line (IPEC-1) as a cell model to study the effect of UL iron on the gut of weaned piglets. Weaned piglets showed a significant decrease in villus height after feeding on a UL iron diet (P < 0.05). The protein levels of DMT1 and Zip14 decreased, and the protein levels of ferritin increased in the duodenal mucosa (P < 0.05) of UL iron fed weaned piglets. Moreover, UL iron also increased the content of ROS and malondialdehyde and decreased the activity of superoxide dismutase in the duodenal mucosa of weaned piglets (P < 0.05). The addition of UL iron to the diet significantly reduced the expression of tight junction proteins Claudin-1, Occludin, and ZO-1 in the duodenal mucosa of weaned piglets (P < 0.05). In the IPEC-1 cell model, iron induced the production of cytosolic and mitochondrial ROS and reduced the mitochondrial membrane potential, which in turn led to cellular vacuolation and fibrosis. Furthermore, UL iron significantly altered the cecum flora of weaned piglets, and the relative abundance of Clostridiales, Faecalibacterium, and Prevotellaceae decreased significantly (P < 0.05), while the relative abundance of Desulfovibrio and Anaerovibrio increased significantly (P < 0.05). In conclusion, UL iron caused damage to the intestinal villi, induced oxidative stress, reduced iron absorption protein, damaged the intestinal barrier, and modified the intestinal microbial structure in weaned piglets.
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Inflammation decreases iron absorption by stimulating hepcidin production and secretion and decreasing DMT-1 protein levels.
“Inflammation in turn decreases iron absorption by stimulating hepcidin production and secretion and decreasing DMT-1 protein levels [39].”
From Oral Iron Supplementation—Gastrointestinal Side Effects and the Impact on the Gut Microbiota (2021) · cites this paper as [39]
The Discussion (page unavailable) reports that excess iron lowered DMT1 expression and duodenal iron uptake in weaned piglets. It does not attribute those changes to inflammation or report that inflammation stimulates hepcidin production and secretion. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn the gastrointestinal tract, this can cause oxidative stress to intestinal cells, causing damage to membrane proteins and lipid peroxidation.
“In the GI tract, this can cause oxidative stress to the intestinal cells causing damage to membrane proteins and lipid peroxidation [39].”
From Oral Iron Supplementation—Gastrointestinal Side Effects and the Impact on the Gut Microbiota (2021) · cites this paper as [39]
Section 3.3 reports oxidative stress and increased malondialdehyde, a marker of lipid peroxidation, in the duodenal mucosa of weaned piglets given upper-limit iron. It also reports reduced tight-junction proteins, but does not establish oxidative damage to membrane proteins; protein carbonylation did not differ significantly from controls. The claim is therefore supported for oxidative stress and lipid peroxidation, but not for the specified protein damage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn the Fenton reaction, reactive oxygen species such as hydrogen peroxide are reduced by electrons to produce free radical species such as hydroxyl ions.
“In the Fenton reaction, reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) are reduced by electrons to produce free radical species such as hydroxyl ions (OH -) [37,39].”
From Oral Iron Supplementation—Gastrointestinal Side Effects and the Impact on the Gut Microbiota (2021) · cites this paper as [39]
The discussion under “Divalent metal ion transporter 1 (DMT-1) plays a role in” says iron-catalyzed Fenton reactions produce active oxygen. It does not specify hydrogen peroxide, electron reduction, or hydroxyl ions as a product of the reaction. (LLM, conf=0.84)
Experimental — accuracy not yet measuredExcess iron in the gastrointestinal tract can cause damage to intestinal villi, resulting in a decrease in height, shape, and stability, along with damage to tight junction proteins between mucosal enterocytes.
“Therefore, when there is excess iron in the gastrointestinal tract, it can cause damage to intestinal villi resulting in a decrease in height, shape, and stability, along with damage to tight junction proteins between the mucosal enterocytes [39].”
From Oral Iron Supplementation—Gastrointestinal Side Effects and the Impact on the Gut Microbiota (2021) · cites this paper as [39]
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Oral Iron Supplementation—Gastrointestinal Side Effects and the Impact on the Gut Microbiota
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“Inflammation in turn decreases iron absorption by stimulating hepcidin production and secretion and decreasing DMT-1 protein levels [39].”
BackgroundInfluential
- Authors
- Ding, H., Yu, X., Chen, L., Han, J., Zhao, Y., & Feng, J.
- Affiliations
- Zhejiang University (CN)
- Corresponding author
- Feng, Jie
- Venue
- Metallomics
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-06-25
- Volume
- 12
- Issue
- 9
- Pages
- 1356-1369
- ISSN
- 1756-5901 (ISSN-L)
- 1756-591X
- OpenAlex
- W3033594857
- Cited by
- 33
- References
- 71
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 6 · 2023: 6 · 2022: 3 · 2021: 6 · 2020: 2
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Metallomics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Basic Research Program of China (2016YFD0501201)
- National Natural Science Foundation of China (31772607)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- tolerable upper intake level, iron supplementation, weaned piglets, intestinal injury, intestinal barrier, tight junction proteins, oxidative stress, intestinal villi, iron absorption, DMT1, ZIP14, ferritin, gut microbiota, cecal microbiota, IPEC-1 cells, mitochondrial membrane potential, iron deficiency anemia
- MeSH terms
- Gastrointestinal Microbiome, Animals, Animal Feed, Intestines, Iron, Swine, Swine Diseases, Weaning, Anemia, Iron-Deficiency
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